B&NG4

• C's followed by G's will be methylated. At CG sites gene transcription doesn't occur.
• Need demethylation of DNA for development and learning.

acetylation acetylation, phosphorylation phosphorylation, methylation, ubiquitination, and ADP-ribosylation.

Histone acetyyltransferases (HATs) catalyze the transfer of acetyl groups to histone proteins, whereas histone deacetylases (HDACs) cause the removal of acetyl groups.

Histone methylation is initiated by histone methyltransferases (HMTs) such as G9 G9 , whereas histone demethylases ((HDM HDMs) such as LSD1 remove methylation marks.

The integration ofsignalling at the level of epigeneticsis commonly referred to as the histone code (alters histone tail).

changes in histone acetylation and DNA methylation alters specific genes transcription processes and is part of many human cognitive disorders such as AD (APP gene), Rett syndrome (MECP2 gene), schizophrenia (reelin gene).

histone-associated heterochromatin undergoes ERK-dependent regulation and these histone and changes in heterochromatin are necessary for hippocampal LTPand memory formation

MAPK/ERK >CREB ->> CBP brings HAT and may be CBP histone H3 phosphorylation which is associated with changes in behavior and synaptic plasticity

Once ERK is activated it exerts downstream affects such as regulation of excitability and transcription of many genes.

• 1. Conditioned stimulus and unconditioned stimulus to test for association
• 2. context conditioned stimulus and unconditioned stimulus
• 3. shock unconditioned stimulus
• 4.unpaired CS and UCS, explicitly unpaired or random
• 5. tone (cs)

• 1. IEG studies: cFOS levels after training
• 2. electrodes during experiments
• 3. fMRI, PETscans during training
• 4.optogenetics

• Stathmin reveals dissociable roles of the basolateral amygdala in parental and social behaviors
• BLA leads to the positive expression maternal behaviors
• Stathmin somehow effects the positive expression social behaviors
• Stathmin and basolateral amygdala via danger assessment can control in opposite directions maternal and social interactions

• important in pup retrieval (knock out shows deficiency)
• without stathmin social interactions are better (decreases assessment of fear)

The Amygdala and Dentate Gyrus havedifferent roles in maternal behaviors:– the Amygdala controls maternal behaviors both invirggin and p p postpartum mice– the DG controls only in the postpartum phase

• Pup retreival task in the home cage: a female is monitored while retrieving 2-5 day old pups to nest for 20 mins (deficits in stathmin affect pup retrieval by lowering efficiency)
• in open field:
• nest building: less efficient without stathmin or without BLA
• bad at danger assessment with KO and lesion
• DG is involved in maternal behavior for postpartum while amygdala invovled for all, as is BLA

• Social withdrawal (cortex, hippocampus, amygdala)– Can be tested by social interactions, social recognition, ultrasonic vocalizations (pup retrieval), juvenile play

• Repetitive behaviors (cerebellum)

• Unable to read social mind (mirror neurons in the cortex)– Tested by empathy?

• Inflexibility (hippocampus, cortex)– Tested by the reversal of the platform in the Morris water maze

• Lack of “social brain” (amygdala-related):
• • The ability to imitate
• • Understand emotions of others
• • Lack of social skills
• • Trustworthiness

PTEN, MET, MECP2, FMR1 and neurotransmission genes.

Pathways in the amygdala, hippocampal, perirhinal cortex areas

• 1. synthesized by a neuron
• 2. present in the presynaptic terminal and taken up by the post (local)
• 3. released as a drug and mimics actions of endogenous neurotrans
• 4. specific mechanism for removal exists(transporter)

• 1. small molecule
• 2. neuroactive peptide

• Parkinson's Disease (caused by loss of dopamine-secreting neurons in the substantia nigra),
• Schizophrenia (involves elevated levels of dopamine activity in the mesolimbic pathway and decreased levels of dopamine in the prefrontal cortex),
• ADHD (associated with decreased dopamine activity).
• Addiction: drugs of abuse (cocaine, amphetamine, opiates, and nicotine) act as positive reinforcers. They increase the level of DA released at terminals of the projections of the ventral tegmental area (VTA). Cocaine and amphetamine do so by blocking the DA transporter

: two DA systems are disturbed in schizophrenia. First, an increase in activity in the mesolimbic (striatum) pathway (likely through D2, D3 and D4-R) would account for the positive symptoms.

Second, decreased activity of the mesocortical connections in the prefrontal cortex would account for negative symptoms. Thus, unbalance between these two systems, cortical and subcorticaldopaminergic transmission underlies the development of schizophrenia.

• Tone and shock at the same time. US & CS paired.
• AMYGDALA

• tone THEN shock. separated (5, 30 60 sec)
• HIPPOCAMPUS, AMYGDALA, CINGULATE GYRUS AND PERIRHINAL CORTEX.

Directly activating a subset of cells through optogenetical stimulation that are involved in the formation of memory is enough to induce the behavioral expression of memory.